词条 | Polycomb recruitment in X chromosome inactivation |
释义 |
XCI is usually divided in two phases, the establishment phase when gene silencing is reversible, and maintenance phase when gene silencing becomes irreversible.[2] During the establishment phase of X Chromosome Inactivation (XCI), Xist RNA, the master regulator of this process, spreads in cis along the future inactive X (Xi) and recruits repressive chromatin-remodelling complexes.[3] Among these, Xist recruits proteins of the Polycomb repressive complexes.[4][5] Whether Xist directly recruits Polycomb repressive complex 2 (PRC2) to the chromatin[6] or this recruitment is the consequence of Xist-mediated changes on the chromatin has been object of intense debate.[7] Some studies showed that PRC2 components are not associated with Xist RNA or do not interact functionally.[8][9][10][11] However another study has shown by means of mass spectrometry analysis,[12] that two subunits of PRC2 may interact with Xist, although these proteins are also found in other complexes and are not unique components of the PRC2 complex. Biochemical studies have also shown that in vitro PRC2 binds the A-repeat (RepA) of Xist RNA directly and with very high affinity (dissociation constants of 10-100 nanomolar),[13][14] supporting Xist-mediated recruitment of PRC2 to the X chromosome. However it is not clear whether such interactions occurs in vivo under physiological conditions. Failure to turn up PRC2 proteins in function screens may be due to cells not being able to survive or compete without PRC2 or incomplete screens. Two super resolution microscopy analyses have presented different views from each other. One showed that Xist and PRC2 are spatially separated,[15] while another showed that Xist and PRC2 are tightly linked.[16] It is possible that several mechanisms recruit PRC2 in parallel, including direct Xist-mediated recruitment, adaptor proteins, chromatin changes, RNA pol II exclusion, or PRC1 recruitment.[17][18] For instance, PRC2 recruitment is linked to PRC1-mediated H2A119 ubiquitination in differentiating embryonic stem cells (ESCs).[19][20][21] where PRC1 recruitment is mediated by hnrnpK and Xist repB [20][21]. In fully differentiated cells, PRC2 recruitment seems to be dependent on Xist RepA.[22] It is possible that alternative and complementary pathways work to establish PRC2 recruitment on the X in different experimental systems and during different stages of development. References1. ^{{cite journal | vauthors = Nora EP, Heard E | title = X chromosome inactivation: when dosage counts | journal = Cell | volume = 139 | issue = 5 | pages = 865–7 | date = November 2009 | pmid = 19945374 | doi = 10.1016/j.cell.2009.11.009 }} 2. ^{{cite journal | vauthors = Wutz A, Jaenisch R | title = A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation | journal = Molecular Cell | volume = 5 | issue = 4 | pages = 695–705 | date = April 2000 | pmid = 10882105 | doi = 10.1016/s1097-2765(00)80248-8 }} 3. ^{{cite journal | vauthors = Chow J, Heard E | title = X inactivation and the complexities of silencing a sex chromosome | journal = Current Opinion in Cell Biology | volume = 21 | issue = 3 | pages = 359–66 | date = June 2009 | pmid = 19477626 | doi = 10.1016/j.ceb.2009.04.012 }} 4. ^{{cite journal | vauthors = de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, Koseki H, Brockdorff N | title = Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation | journal = Developmental Cell | volume = 7 | issue = 5 | pages = 663–76 | date = November 2004 | pmid = 15525528 | doi = 10.1016/j.devcel.2004.10.005 }} 5. ^{{cite journal | vauthors = Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y | title = Role of histone H3 lysine 27 methylation in X inactivation | journal = Science | volume = 300 | issue = 5616 | pages = 131–5 | date = April 2003 | pmid = 12649488 | doi = 10.1126/science.1084274 }} 6. ^{{cite journal | vauthors = Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT | title = Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome | journal = Science | volume = 322 | issue = 5902 | pages = 750–6 | date = October 2008 | pmid = 18974356 | pmc = 2748911 | doi = 10.1126/science.1163045 }} 7. ^{{cite journal | vauthors = Cerase A, Smeets D, Tang YA, Gdula M, Kraus F, Spivakov M, Moindrot B, Leleu M, Tattermusch A, Demmerle J, Nesterova TB, Green C, Otte AP, Schermelleh L, Brockdorff N | title = Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 6 | pages = 2235–40 | date = February 2014 | pmid = 24469834 | pmc = 3926064 | doi = 10.1073/pnas.1312951111 }} 8. ^{{cite journal | vauthors = Chu C, Zhang QC, da Rocha ST, Flynn RA, Bharadwaj M, Calabrese JM, Magnuson T, Heard E, Chang HY|authorlink9=Howard Y. Chang | title = Systematic discovery of Xist RNA binding proteins | journal = Cell | volume = 161 | issue = 2 | pages = 404–16 | date = April 2015 | pmid = 25843628 | pmc = 4425988 | doi = 10.1016/j.cell.2015.03.025 }} 9. ^{{cite journal | vauthors = McHugh CA, Chen CK, Chow A, Surka CF, Tran C, McDonel P, Pandya-Jones A, Blanco M, Burghard C, Moradian A, Sweredoski MJ, Shishkin AA, Su J, Lander ES, Hess S, Plath K, Guttman M | title = The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3 | journal = Nature | volume = 521 | issue = 7551 | pages = 232–6 | date = May 2015 | pmid = 25915022 | pmc = 4516396 | doi = 10.1038/nature14443 }} 10. ^{{cite journal | vauthors = Moindrot B, Cerase A, Coker H, Masui O, Grijzenhout A, Pintacuda G, Schermelleh L, Nesterova TB, Brockdorff N | title = A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing | journal = Cell Reports | volume = 12 | issue = 4 | pages = 562–72 | date = July 2015 | pmid = 26190105 | pmc = 4534822 | doi = 10.1016/j.celrep.2015.06.053 }} 11. ^{{cite journal | vauthors = Monfort A, Di Minin G, Postlmayr A, Freimann R, Arieti F, Thore S, Wutz A | title = Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells | journal = Cell Reports | volume = 12 | issue = 4 | pages = 554–61 | date = July 2015 | pmid = 26190100 | pmc = 4530576 | doi = 10.1016/j.celrep.2015.06.067 }} 12. ^{{cite journal|vauthors=Minajigi A, Froberg J, Wei C, Sunwoo H, Kesner B, Colognori D, Lessing D, Payer B, Boukhali M, Haas W, Lee JT|date=July 2015|title=Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation|journal=Science|volume=349|issue=6245|doi=10.1126/science.aab2276|pmc=4845908|pmid=26089354}} 13. ^{{cite journal | vauthors = Cifuentes-Rojas C, Hernandez AJ, Sarma K, Lee JT | title = Regulatory interactions between RNA and polycomb repressive complex 2 | journal = Molecular Cell | volume = 55 | issue = 2 | pages = 171–85 | date = July 2014 | pmid = 24882207 | pmc = 4107928 | doi = 10.1016/j.molcel.2014.05.009 }} 14. ^{{cite journal | vauthors = Davidovich C, Wang X, Cifuentes-Rojas C, Goodrich KJ, Gooding AR, Lee JT, Cech TR | title = Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA | journal = Molecular Cell | volume = 57 | issue = 3 | pages = 552–8 | date = February 2015 | pmid = 25601759 | pmc = 4320675 | doi = 10.1016/j.molcel.2014.12.017 }} 15. ^{{cite journal | vauthors = Cerase A, Pintacuda G, Tattermusch A, Avner P | title = Xist localization and function: new insights from multiple levels | journal = Genome Biology | volume = 16 | pages = 166 | date = August 2015 | pmid = 26282267 | pmc = 4539689 | doi = 10.1186/s13059-015-0733-y }} 16. ^{{cite journal | vauthors = Sunwoo H, Wu JY, Lee JT | title = The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 31 | pages = E4216-25 | date = August 2015 | pmid = 26195790 | pmc = 4534268 | doi = 10.1073/pnas.1503690112 }} 17. ^{{cite journal | vauthors = Pintacuda G, Cerase A | title = X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells | journal = Stem Cell Reviews | volume = 11 | issue = 5 | pages = 699–705 | date = October 2015 | pmid = 26198263 | pmc = 4561061 | doi = 10.1007/s12015-015-9597-5 }} 18. ^{{cite journal | vauthors = Pinter SF | title = A Tale of Two Cities: How Xist and its partners localize to and silence the bicompartmental X | journal = Seminars in Cell & Developmental Biology | volume = 56 | pages = 19–34 | date = August 2016 | pmid = 27072488 | doi = 10.1016/j.semcdb.2016.03.023 }} 19. ^{{cite journal | vauthors = Almeida M, Pintacuda G, Masui O, Koseki Y, Gdula M, Cerase A, Brown D, Mould A, Innocent C, Nakayama M, Schermelleh L, Nesterova TB, Koseki H, Brockdorff N | title = PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation | journal = Science | volume = 356 | issue = 6342 | pages = 1081–1084 | date = June 2017 | pmid = 28596365 | doi = 10.1126/science.aal2512 }} 20. ^1 {{cite journal | vauthors = Pintacuda G, Wei G, Roustan C, Kirmizitas BA, Solcan N, Cerase A, Castello A, Mohammed S, Moindrot B, Nesterova TB, Brockdorff N | title = hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb-Mediated Chromosomal Silencing | journal = Molecular Cell | volume = 68 | issue = 5 | pages = 955–969.e10 | date = December 2017 | pmid = 29220657 | pmc = 5735038 | doi = 10.1016/j.molcel.2017.11.013 }} 21. ^1 {{cite journal | vauthors = Pintacuda G, Young AN, Cerase A | title = Function by Structure: Spotlights on Xist Long Non-coding RNA | journal = Frontiers in Molecular Biosciences | volume = 4 | pages = 90 | date = 2017 | pmid = 29302591 | pmc = 5742192 | doi = 10.3389/fmolb.2017.00090 }} 22. ^{{cite journal | vauthors = Pintacuda G, Young AN, Cerase A | title = Function by Structure: Spotlights on Xist Long Non-coding RNA | journal = Frontiers in Molecular Biosciences | volume = 4 | pages = 90 | date = 2017 | pmid = 29302591 | pmc = 5742192 | doi = 10.3389/fmolb.2017.00090 }} 1 : Cell biology |
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